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This article studies the formation of Early Modern historiography through examining the theories, methods and functions of one of its most conspicuous and relevant types, that which investigates the origins of historical entities and facts. By focussing both on the artes historicae and on a wide range of accounts about the foundation of cities, the invention of arts or the causes of wars, this article illustrates how Renaissance writers construct a scientific paradigm which sanctions the ideological, philosophical and rhetorical forms, purposes and values of the narrative of the origins and allows to understand that it is precisely because of its principles and methods that this kind of stories are so characteristic of Early Modern historiography.

Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neurological disorders, affecting either axons from the motor and/or sensory neurons or Schwann cells of the peripheral nervous system (PNS) and caused by more than 100 genes. We previously identified mutations in FGD4 as responsible for CMT4H, an autosomal recessive demyelinating form of CMT disease. FGD4 encodes FRABIN, a GDP/GTP nucleotide exchange factor, particularly for the small GTPase Cdc42. Remarkably, nerves from patients with CMT4H display excessive redundant myelin figures called outfoldings that arise from focal hypermyelination, suggesting that FRABIN could play a role in the control of PNS myelination. To gain insights into the role of FGD4/FRABIN in Schwann cell myelination, we generated a knockout mouse model (Fgd4SC-/-), with conditional ablation of Fgd4 in Schwann cells. We show that the specific deletion of FRABIN in Schwann cells leads to aberrant myelination in vitro, in dorsal root ganglia neuron/Schwann cell co-cultures, as well as in vivo, in distal sciatic nerves from Fgd4SC-/- mice. We observed that those myelination defects are related to an upregulation of some interactors of the NRG1 type III/ERBB2/3 signalling pathway, which is known to ensure a proper level of myelination in the PNS. Based on a yeast two-hybrid screen, we identified SNX3 as a new partner of FRABIN, which is involved in the regulation of endocytic trafficking. Interestingly, we showed that the loss of FRABIN impairs endocytic trafficking, which may contribute to the defective NRG1 type III/ERBB2/3 signalling and myelination. Using RNA-Seq, in vitro, we identified new potential effectors of the deregulated pathways, such as ERBIN, RAB11FIP2 and MAF, thereby providing cues to understand how FRABIN contributes to proper ERBB2 trafficking or even myelin membrane addition through cholesterol synthesis. Finally, we showed that the re-establishment of proper levels of the NRG1 type III/ERBB2/3 pathway using niacin treatment reduces myelin outfoldings in nerves of CMT4H mice. Overall, our work reveals a new role of FRABIN in the regulation of NRG1 type III/ERBB2/3 NRG1signalling and myelination and opens future therapeutic strategies based on the modulation of the NRG1 type III/ERBB2/3 pathway to reduce CMT4H pathology and more generally other demyelinating types of CMT disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: High preoperative fibrinogen levels are associated with reduced bleeding rates after cardiac surgery. Fibrinogen is directly involved in inflammatory processes and is a cardiovascular risk factors. Whether high fibrinogen levels before cardiac surgery are a risk factor for mortality or morbidity remains unclear., Aims: This study aimed to examine the association between preoperative fibrinogen levels and mortality and morbidity rates after cardiac surgery., Settings and Design: This is a single-center retrospective study., Material and Methods: Patients (n = 1628) were divided into high (HFGr) and normal (NFGr) fibrinogen level groups, based on the cutoff value of 3.3 g/L, derived from the receiver operating characteristic (ROC) curve analysis. The primary outcome was the 30-day mortality rate. The rates of postoperative complications, including postoperative bleeding and transfusion rates, were examined., Statistical Analysis: Between-group comparisons were performed with the Mann-Whitney U test and Chi-squared test, as suitable. Model discriminative power was examined with the area under the ROC curve., Results: The HFGr and NFGr included 1103 and 525 patients, respectively. Mortality rate was higher in the HFGr than in the NFGr (2.7% vs. 1.1%, P = 0.04). The 12-h bleeding volume (280 mL [195-400] vs. 305 mL [225-435], P = 0.0003) and 24-h bleeding volume values (400 mL [300-550] vs. 450 mL [340-620], P < 0.0001) were lower in the HFGr than in the NFGr. However, the rate of red blood cell transfusion during hospitalization was higher in the HFGr than in the NFGr (21.7% vs. 5.9%, P = 0.0103). Major complications were more frequent in the HFGr than in the NFGr., Conclusion: High fibrinogen levels were associated with reduced postoperative bleeding volume and increased mortality and morbidity rates.

Cytoplasmic aminoacyl-tRNA synthetases (ARSs) are emerging as a cause of numerous rare inherited diseases. Recently, biallelic variants in tyrosyl-tRNA synthetase 1 (YARS1) have been described in ten patients of three families with multi-systemic disease (failure to thrive, developmental delay, liver dysfunction, and lung cysts). Here, we report an additional subject with overlapping clinical findings, heterozygous for two novel variants in tyrosyl-tRNA synthetase 1 (NM_003680.3(YARS1):c.176T>C; p.(Ile59Thr) and NM_003680.3(YARS1):c.237C>G; p.(Tyr79*) identified by whole exome sequencing. The p.Ile59Thr variant is located in the highly conserved aminoacylation domain of the protein. Compared to subjects previously described, this patient presents a much more severe condition. Our findings support implication of two novel YARS1 variants in these disorders. Furthermore, we provide evidence for a reduced protein abundance in cells of the patient, in favor of a partial loss-of-function mechanism., (Copyright © 2021. Published by Elsevier Masson SAS.)

During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative diagnosis was finally retained (n = 152) with those who had COVID-19 (n = 222). Most common diagnoses were another infectious disease and heart failure. COVID-19-negative patients were more often active smokers had less often cough, fever, and digestive symptoms, as compared to the 222 COVID-19-positive patients. They had higher median neutrophil and lymphocyte counts and lower CRP level. In multivariate analysis, no current smoking, neurocognitive disorder, myalgia, and fibrinogen ≥4g/L were independently associated with a final diagnosis of COVID-19., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Influenza remains a major cause of illness and death in geriatric populations. While the influenza vaccine has successfully reduced morbidity and mortality, its effectiveness is suspected to decrease with age. The aim of this study was to assess the impact of influenza vaccination on all-cause mortality in very old ambulatory subjects. We conducted a prospective cohort study from 1 July 2016 to 31 June 2017 in a large unselected ambulatory population aged over 80 years. We compared all-cause mortality in vaccinated versus unvaccinated subjects after propensity-score matching, to control for age, sex and comorbidities. Among the 9149 patients included, with mean age 86 years, 4380 (47.9%) were vaccinated against influenza. In total, 5253 (57.4%) had at least one chronic disease. The most commonly vaccinated patients were those with chronic respiratory failure (76.3%) and the least commonly vaccinated were those suffering from Parkinson's disease (28.5%). Overall, 2084 patients (22.8%) died during the study. After propensity score matching, the mortality was evaluated at 20.9% in the vaccinated group and 23.9% in the unvaccinated group (OR = 0.84 [0.75-0.93], p = 0.001). This decrease in mortality in the vaccinated group persisted whatever the age and Charlson Comorbidity index. In conclusion, nearly a half of this ambulatory elderly population received Influenza vaccine. After adjustment on comorbidities, influenza vaccination was associated with a significant decrease in all-cause mortality, even in the eldest multimorbid population. Improving immunization coverage in this frail older population is urgently needed.